Myomics' technology to be developed in this Phase 1 project is based upon an in vitro skeletal muscle tissue force measurement technique for high throughput screening (HTS) of compounds to attenuate muscle weakness. The technology, termed Patterned Micro-Post-Arrays (P-uPA), is comprised of bioengineered skeletal muscle tissue attached to micro-mechanical sensors in a 96 well format to detect muscle contractile forces. Miniature human BioArtificial Muscles (mBAMs) are three-dimensional (3-D) contractile tissues with organized striated skeletal muscle fibers which can generate directed force when electrically stimulated. Myomics' mBAM tissue/sensor composite is well suited for repetitive nondestructive force measurements long term i.e. weeks; the sensors provide physiological data regarding tissue function in response to a drug. Such long term studies can determine cumulative effects of drugs on 3-D tissues which are not apparent in shorter term single cell or monolayer HTS technologies. mBAMs have been successfully engineered to grow within the sensors and generate force using P-uPA prototypes. The purpose of this project is to expand these preliminary studies into reproducible quantitative muscle force measurements for up to 30 days. Briefly, Myomics will (1) determine the optimal micro-post geometry for measuring mBAM passive and active contractile forces; (2) test P-uPA with mBAMs chemically stimulated to contract; (3) incorporate in-plane electrodes into the P-uPA technology; and (4) test P-uPA with mBAMs electrically stimulated to contract. With Myomics' P-uPA technology, the physiological measurement of force generation by mBAMs will not be limited to any particular known biochemical pathway and the measurement of force will be the result of both positive and negative drug effects. Thus, the technology will not only screen compounds for positive muscle growth effects, but will more rapidly eliminate target compounds with adverse side effects. This will lead to a greater chance of success in follow-up preclinical animal and Phase 1 clinical studies. Musculoskeletal disorders affect greater than 60 million individuals in the U.S. today and the annual health care costs resulting from skeletal muscle weakness is hundreds of billions of dollars. Few drugs are currently available to treat these disorders and Myomics' high throughput drug screening technology using bioengineered muscle tissue is aimed at identifying new drugs candidates to attenuate skeletal muscle weakness including the sarcopenia associated with aging. [unreadable] [unreadable] [unreadable] [unreadable]